Project Summary While traditional genetic studies to investigate DNA or RNA nucleotide information, epigenetic analyses aim to characterize chemical modifications within both DNA/RNA sequences and histone proteins. Epigenetic changes are preserved during cell division and potentially modify the expression of certain genes instead of altering the genetic code of nucleotide sequences, which is not only due to regular and natural occurrence but also influenced by several factors including age, the environment/lifestyle, and disease status. More importantly, some epigenetic modifications can potentially be transmitted to offspring by transgenerational epigenetic inheritance. Our more recent study suggests that this intergenerational transmission of paternally acquired metabolic disorders is mediated by a nucleic acid modification enzyme called DNA (cytosine-5-)-methyltransferase 2 (Dnmt2). Inspired by these findings, this P50 will focus on the relationship between epigenetic profiles and metabolic disorders in both animal models and human subjects. To study the epigenetic regulation, it is critical to know not only what kinds of modifications are present but also their genomic loci. Therefore, high-throughput sequencing will be applied to profile epigenetic alterations in both animal and human samples. This Epigenomics Core (Core D) will provide essential, cutting edge, bioinformatical expertise to facilitate the translational impact of this highly integrated P50. Firstly, Core D will coordinate outsource library sequencing for individual projects (Specific Aim #1). Secondly, Core D will provide centralized computational service to store, process, and analyze the sequencing data, using our in-house well-characterized pipelines (Specific Aims #2). Finally, Core D will be responsible for hosting an in-house web-based server to share the omics data (Specific Aim #3), which provides both the internal and external researchers an easy access to the data generated from individual projects.